Inhibition of CaMKII Attenuates Progressing Disruption of Ca2+ Homeostasis Upon Left Ventricular Assist Device Implantation in Human Heart Failure

In heart failure, left ventricular assist device (LVAD) implantation is performed to ensure sufficient cardiac output. Whereas some patients are subsequently weaned from LVAD support, other patients still need heart transplantation. To elucidate underlying mechanisms, we assessed the arrhythmogenic SR‐Ca²⁺ leak at the time of LVAD implantation (HF‐Im) and heart transplantation (HF‐Tx) and evaluated the effects of CaMKII‐inhibition. Human left‐ventricular cardiomyocytes were isolated, paced at 1 Hz for 10 beats to ensure SR‐Ca²⁺ loading and scanned for diastolic Ca²⁺ sparks (confocal microscopy). In HF‐Im, the high diastolic spark frequency (CaSpF) of 0.76 ± 0.12 × 100 μm^?1 × s^?1 could be reduced to 0.48 ± 0.10 × 100 μm^?1 × s^?1 by CaMKII inhibition (AIP, 1 μM). The amplitude of Ca²⁺ sparks, width, and length was not significantly altered. In sum, CaMKII inhibition yielded a clear tendency toward a reduction of the SR‐Ca²⁺ leak (n cells/patients = 76/6 vs. 108/6, P = 0.08). In HF‐Tx, we detected an even higher CaSpF of 1.00 ± 0.10 100 μm^?1 × s^?1 and a higher SR‐Ca²⁺ leak compared with HF‐Im (increase by 81 ± 33%, n cells/patients = 156/7 vs. 130/7, P < 0.05), which fits to the further decreased LV function. Here, CaMKII inhibition likewise reduced CaSpF (0.35 ± 0.09 100 μm^?1 × s^?1, P = 0.06) and significantly reduced spark duration (n sparks/patients = 58/3 vs. 159/3, P < 0.05). Conclusively, the SR‐Ca²⁺ leak was reduced by 69 ± 12% in HF‐Tx upon CaMKII inhibition (n cells/patients = 53/3 vs. 91/3, P < 0.05). These data show that the SR‐Ca²⁺ leak correlates with the development of LV function after LVAD implantation and may represent an important pathomechanism. The fact that CaMKII inhibition reduces the SR‐Ca²⁺ leak in HF‐Tx suggests that CaMKII inhibition may be a promising option to beneficially influence clinical course after LVAD implantation.     

Does an Advanced Pelvic Simulation Curriculum Improve Resident Performance on a Pediatric and Adolescent Gynecology Focused Objective Structured Clinical Examination? A Cohort Study

Study ObjectiveTo determine the effect of an advanced pelvic simulation curriculum on resident performance on a pediatric and adolescent gynecology (PAG) focused objective structured clinical examination (OSCE).DesignObstetrics and gynecology residents in a single academic Canadian center participated in a PAG simulation curriculum. An OSCE on prepubertal vaginal bleeding was administered at the biannual OSCE examination 2 months before the simulation curriculum and again 3 months after the simulation curriculum.SettingAcademic half-day at the University of Ottawa Skills and Simulation Centre.ParticipantsObstetrics and gynecology residents from the University of Ottawa.InterventionsParticipants completed 4 stations teaching PAG-appropriate history-taking, genital examination, Tanner staging, vaginal sampling and flushing, hymenectomy, vaginoscopy, laparoscopic adnexal detorsion, and approach to the child and/or adolescent. Advanced pelvic models were used for procedure-specific stations.Main Outcome MeasuresThe primary outcome measure was change in mean score on a prepubertal vaginal bleeding OSCE station. Secondary outcome measures were changes in individual component scores.ResultsFourteen residents completed the simulation curriculum and the PAG OSCE at the 2 separate time points (before and after simulation curriculum). The mean OSCE score before the simulation curriculum was 54.6% (20.5 of 37) and mean score after the curriculum was 78.1% (28.9 of 37; P < .001). Significant score increases were found in history-taking, examination, differential diagnosis, identification of organism, surgical procedures, and identification of foreign body (P < .01 for all).ConclusionThis innovative PAG simulation curriculum significantly increased residents' knowledge in PAG history-taking, examination skills, operative procedures, and approach to the child and/or adolescent. Obstetrics and Gynecology Program Directors should consider incorporating PAG simulation training into their curriculum to ensure that residents meet their learning objectives and increase their knowledge and confidence, which will ultimately benefit patient care.     

Meniett低压脉冲治疗仪治疗梅尼埃病的系统评价

目的：系统评价Meniett低压脉冲治疗仪对治疗梅尼埃病的影响。方法计算机检索Pubmed、Web of Science、Cochrane Library、CNKI及万方数据库,搜索限于建库至2015年12月。按照纳入和排除标准筛选文献,由2位评价员独立进行资料评价、提取、剔除/引用、最后再进行核对,应用review manager 5.2版软件对最后纳入研究进行Meta分析。结果按照纳入标准,最终纳入英文文献14篇,中文文献1篇,共474例病例。符合Meta分析文献13篇,结果显示对平均纯音听阈的影响[MD=3.31,95%CI（1.29,5.33）],眩晕发作频率的影响[MD=6.81,95%CI（4.62,9.01）],AAO-HNS功能评分的影响[MD=0.63,95%CI （-4.13,5.39）]。结论对于传统药物治疗无效的梅尼埃病,Meniett低压脉冲治疗仪是一种微创性、非结构破坏性和安全有效的治疗方法。